Osmotic pump with means for dissipating internal pressure

ABSTRACT

The present invention includes an osmotic pump that includes a means for venting an osmotic composition included in the pump before the internal pressure of the pump has the opportunity to build to such an extent that the pump is structurally compromised, such as when one or more components of the pump are physically separated. The means for venting osmotic material included in an osmotic pump according to the present invention includes a vent that allows the material included in the osmotic composition of the pump to dissipate into an environment of operation at a rate that results in dissipation of the pressure created within the osmotic pump and a reduced potential for subject discomfort or irritation.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of application Ser. No. 10/814,801,filed Mar. 31, 2004, pending, which claims the benefit of the filingdate of provisional patent application Ser. No. 60/459,296, filed Mar.31, 2003, for “Osmotic Pump With Means For Dissipating InternalPressure.” The disclosure of each of the previously referenced U.S.patent applications is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to implantable osmotic pumps providingsustained delivery of a drug. In particular, the present invention isdirected to an implantable osmotic pump including a vent that allowsgradual venting of osmotic material after the drug formulation includedin the osmotic pump is delivered.

BACKGROUND

Implantable, controlled-release osmotic pumps (hereinafter “osmoticpumps”) are known in the art. For example, U.S. Pat. Nos. 3,797,492,3,987,790, 4,008,719, 4,865,845, 5,057,318, 5,059,423, 5,112,614,5,137,727, 5,151,093, 5,234,692, 5,234,693, 5,279,608, 5,336,057,5,728,396, 5,985,305, 5,997,527, 5,997,902, 6,113,938, 6,132,420,6,217,906, 6,261,584, 6,270,787, and 6,375,978, which are assigned toALZA Corporation of Mountain View, Calif., and are herein incorporatedin their entirety by reference, describe various osmotic pumps. Theosmotic pumps described in these references may be designed forimplantation in a subject of choice and may be configured to deliver arange of drugs at various rates over predetermined periods of time.

Osmotic pumps typically include a reservoir for containing an amount ofdrug formulation, an osmotic composition, a semipermeable membrane, adelivery orifice, and a piston separating the drug formulation from theosmotic composition. Upon administration to an environment of operation,water is drawn through the semipermeable membrane of the osmotic pumpinto the osmotic composition, causing the osmotic composition to swell.As the osmotic composition swells, the piston included in the osmoticpump is driven through its stroke, resulting in the expulsion of thedrug formulation at a controlled rate through the delivery orifice. Therate of drug release from an osmotic pump may be adjusted by alteringthe composition or amount of the drug formulation or the osmoticcomposition included in the osmotic pump. Alternatively, the releaserate of drug formulation provided by an osmotic pump may be adjusted byaltering the composition or exposed surface area of the semipermeablemembrane. Because they allow the controlled delivery of active agentover periods of weeks, months, or even years, osmotic pumps canadvantageously provide long-term dosing of a desired drug withoutrequiring frequent visits to a healthcare provider or repetitiveself-medication. Therefore, osmotic pumps can work to provide increasedpatient compliance, reduced irritation at the site of administration,fewer occupational hazards for healthcare providers, reduced wastehazards, and increased therapeutic efficacy through enhanced dosingcontrol.

As drug formulation is delivered from an osmotic pump, the internalpressure generated by the osmotic composition within the pump generallyremains relatively low. However, if an osmotic system is left within anenvironment of operation after the piston included in the osmotic pumpreaches the end of its stroke within the reservoir (e.g., aftersubstantially all the drug formulation has been delivered), the osmoticcomposition will continue to draw water in from the environment ofoperation. As water is drawn into the osmotic pump without expulsion ofa corresponding amount of drug formulation, the pressure within thesystem may rise to such an extent that a component of the osmotic pumpis compromised or physically separated. Where the semipermeable membraneincluded in an osmotic pump is held in place through a friction fit,such as is described in, for example, U.S. Pat. Nos. 5,985,305,5,728,396, and 6,156,331, the semipermeable membrane is one of thecomponents that is most likely to be separated from the osmotic pump ifthe internal pressure of the osmotic system increases well beyond normaloperational pressures.

It would, therefore, be an improvement in the art to provide an osmoticpump that allows the placement of a semipermeable membrane through afriction fit mechanism, yet works to prevent a pressure build-up withinthe pump that results in the dissociation of pump components, such asthe semipermeable membrane. Though not likely to be harmful to asubject, the physical separation of one or more components of animplanted osmotic pump may complicate removal of the device from asubject. Moreover, the physical separation of the semipermeable membraneof an osmotic pump may allow a relatively sudden release of the materialforming the osmotic composition, which may result in localizeddiscomfort or inflammation. Thus, where an implantable osmotic pump isdesigned to dissipate internal pressure before such pressure reaches alevel that could cause dissociation of one or more parts, the design ofthe osmotic pump would ideally allow pressure dissipation withoutcausing a release of osmotic material that results in discomfort orinflammation.

SUMMARY OF THE INVENTION

The present invention is directed to an osmotic pump that includes ameans for venting the osmotic composition included therein before theinternal pressure of the pump has the opportunity to build to such anextent that the pump is structurally compromised, such as when one ormore components of the pump are physically separated. The means forventing osmotic material included in an osmotic pump according to thepresent invention includes a vent that allows the material included inthe osmotic composition of the pump to dissipate into an environment ofoperation, resulting in a reduction of the internal pressure

The vent included in an osmotic pump of the present invention is formedthrough the reservoir of the osmotic pump and is positioned such thatthe vent is sealed from the osmotic composition under normal operatingconditions. However, the vent is also positioned in the reservoir suchthat, if the pressure within the osmotic pump reaches a magnitude thatresults in displacement of one or more components, the vent is opened orexposed to the materials forming the osmotic composition, which allowsrelease of materials forming the osmotic composition into theenvironment of operation and results in the dissipation of the internalpressure before one or more components of the osmotic pump fails or isseparated from the device. In addition, because an osmotic pumpaccording to the present invention can be designed without compressiveelements, the maximum rate of material expulsion from the vent willtypically match the targeted release rate of the osmotic pump.Therefore, an osmotic pump according to the present invention can beeasily designed to allow venting of the osmotic composition, whilereducing or minimizing the likelihood that such venting will result indiscomfort or irritation to the subject.

In a preferred embodiment, an osmotic pump includes a vent that issealed by the semipermeable membrane of the osmotic pump during normaloperating conditions. The semipermeable membrane of such an embodimentis friction fit within the reservoir and is designed to allowprogressive displacement of the semipermeable membrane once a thresholdpressure is reached within the osmotic pump. The vent included in thisembodiment of the present invention is positioned such that, if theinternal pressure reaches the threshold pressure and the semipermeablemembrane begins to be displaced relative to the reservoir, the vent isexposed well before the semipermeable membrane is separated from thedevice. Once the vent is exposed, the osmotic materials included in theosmotic composition may be expelled from the osmotic pump, resulting ina decrease in pressure within the pump and preventing separation of thesemipermeable membrane.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention is described with reference to the accompanyingdrawings in which like elements bear like reference numerals, andwherein:

FIG. 1 provides a schematic illustration of one embodiment of an osmoticpump according to the present invention.

FIG. 2 provides a schematic illustration of the osmotic pump shown inFIG. 1 as the pump functions to deliver drug formulation to anenvironment of operation.

FIG. 3 provides a schematic illustration of the osmotic pump shown inFIG. 1 and FIG. 2 as delivery of the drug formulation is completed andthe piston included in the osmotic pump reaches the end of its strokewithin the reservoir.

FIG. 4 provides a schematic illustration of the osmotic pump shown inFIG. 1 through FIG. 3 after the internal pressure of the osmotic pumphas caused displacement of the semipermeable membrane, the vent has beenexposed, and the osmotic composition is venting into the environment ofoperation.

DETAILED DESCRIPTION OF THE INVENTION

An osmotic pump 10 according to the present invention is illustrated inFIG. 1. As can be seen by reference to these figures, an osmotic pump 10according to the present invention includes a reservoir 12, a drugformulation 14, an osmotic composition 16, a piston 18, a semipermeablemembrane 22, a delivery orifice 24, and a vent 26 formed through thewall 20 of the reservoir 12. However, the configuration of the osmoticpump 10 illustrated in FIG. 1 provides only one example of an osmoticpump according to the present invention and is not to be construed aslimiting the present invention. The present invention is generallyapplicable to osmotic pumps, and an osmotic pump according to thepresent invention may be designed to conform to a wide range of desiredsizes or shapes. Moreover, an osmotic pump according to the presentinvention may be designed for application in various environments oradministration by various routes, such as by oral administration,ruminal administration, or implantation.

The reservoir 12 of the osmotic pump 10 of the present invention may besized and shaped as desired to suit a desired application or tofacilitate placement of the osmotic pump 10 in a desired environment ofoperation. Materials suitable for forming the reservoir 12 must besufficiently strong to ensure that the reservoir 12 does not leak,crack, break, or significantly distort under stresses to which it issubjected to during administration and operation of the osmotic pump 10.In particular, the reservoir 12 is formed of a material that issufficiently rigid to withstand expansion of the osmotic composition 16without undergoing substantial changes to the size or shape of thereservoir 12. The material used to form the reservoir 12 is also chosento be largely impermeable to fluids from the environment of operationand to the material constituents included in the drug formulation 14 andthe osmotic composition 16. As it is used herein the term “largelyimpermeable” indicates that the migration of materials into or out ofthe osmotic pump through the material forming the reservoir 12 is so lowthat any such migration of materials has substantially no adverse impacton the function of the device.

The material used to form the reservoir 12 of an osmotic pump 10according to the present invention is preferably not a bioerodiblematerial and will remain intact even after the drug formulation 14 hasbeen delivered. Such a design facilitates recovery or passage of theosmotic pump 10 after the drug formulation 14 contained therein has beendelivered to a subject. Typical materials suitable for the constructionof the reservoir 12 of an osmotic pump 10 according to the presentinvention include, but are not limited to, nonreactive polymers andbiocompatible metals and alloys. Specific examples of suitable polymersinclude, but are not limited to, polyimide, polysulfone, polycarbonate,polyethylene, polypropylene, polyvinylchloride-acrylic copolymer,polycarbonate-acrylonitrile-butadiene-styrene, polystyrene,acrylonitrile polymers, such as acrylonitrile-butadiene-styreneterpolymer and the like, halogenated polymers, such aspolytetrafluoroethylene, polychlorotrifluoroethylene copolymer,tetrafluoroethylene and hexafluoropropylene. Metallic materials usefulin forming the reservoir 12 include, but are not limited to, stainlesssteel, titanium, platinum, tantalum, gold, and their alloys, as well asgold-plated ferrous alloys, platinum-plated ferrous alloys,cobalt-chromium alloys, and titanium nitride coated stainless steel.

The semipermeable membrane 22 included in an osmotic pump 10 of thepresent invention is formulated and prepared to be permeable to thepassage of external liquids, such as water and biological liquids, butsubstantially impermeable to the passage of the drug, osmopolymers,osmagents, and the like that may be included in the osmotic pump 10.Suitable materials and methods for forming the semipermeable membrane 22included in an osmotic pump 10 of the present invention are well knownin the art and are detailed in, for example, U.S. Pat. Nos. 3,797,492,3,987,790, 4,008,719, 4,865,845, 4,874,388, 5,057,318, 5,059,423,5,112,614, 5,137,727, 5,151,093, 5,234,692, 5,234,693, 5,279,608,5,336,057, 5,728,396, 5,985,305, 5,997,527, 5,997,902, 6,113,938,6,132,420, 6,217,906, 6,261,584, 6,270,787, and 6,375,978, the contentsof which are herein incorporated in their entirety by this reference.Such possible semipermeable materials from which the semipermeablemembrane 22 can be made include, but are not limited to, for example,Hytrel polyester elastomers (DuPont), cellulose esters, celluloseethers, and cellulose ester-ethers, water flux enhanced ethylene-vinylacetate copolymers, semipermeable membranes made by blending a rigidpolymer with water-soluble low molecular weight compounds, and othersemipermeable materials well known in the art. The above cellulosicpolymers have a degree of substitution, D.S., on the anhydroglucoseunit, from greater than 0 up to 3 inclusive. By “degree ofsubstitution,” or “D.S.,” is meant the average number of hydroxyl groupsoriginally present on the anhydroglucose unit comprising the cellulosepolymer that is replaced by a substituting group. Representativematerials include, but are not limited to, one selected from the groupconsisting of cellulose acylate, cellulose diacylate, cellulosetriacylate, cellulose acetate, cellulose diacetate, cellulosetriacetate, mono-, di-, and tricellulose alkanylates, mono-, di-, andtricellulose aroylates, and the like. Exemplary cellulosic polymersinclude cellulose acetate having a D.S. up to 1 and an acetyl content upto 21%; cellulose acetate having a D.S. of 1 to 2 and an acetyl contentof 21% to 35%; cellulose acetate having a D.S. of 2 to 3 and an acetylcontent of 35% to 44.8%, and the like. More specific cellulosic polymersinclude cellulose propionate having a D.S. of 1.8 and a propionylcontent of 39.2% to 45% and a hydroxyl content of 2.8% to 5.4%;cellulose acetate butyrate having a D.S. of 1.8 and an acetyl content of13% to 15% and a butyryl content of 34% to 39%; cellulose acetatebutyrate having an acetyl content of 2% to 29%, a butyryl content of 17%to 53%, and a hydroxyl content of 0.5% to 4.7%; cellulose acetatebutyrate having a D.S. of 1.8, an acetyl content of 4% average weightpercent, and a butyryl content of 51%; cellulose triacylates having aD.S. of 2.9 to 3 such as cellulose trivalerate, cellulose trilaurate,cellulose tripalmitate, cellulose trisuccinate, and cellulosetrioctanoate; cellulose diacylates having a D.S. of 2.2 to 2.6 such ascellulose disuccinate, cellulose dipalmitate, cellulose dioctanoate,cellulose dipentate; coesters of cellulose, such as cellulose acetatebutyrate and cellulose, cellulose acetate propionate, and the like.Other materials that may be used to prepare a semipermeable membrane 22useful in the osmotic pump 10 of the present invention includepolyurethane, polyetherblockamide (PEBAX, commercially available fromELF ATOCHEM, Inc.), and injection-moldable thermoplastic polymers withsome hydrophilicity such as ethylene vinyl alcohol (EVA).

The osmotic composition 16 included in the osmotic pump 10 of thepresent invention may be formed of any material that creates sufficientosmotic pressure to draw water into the osmotic composition 16 throughthe semipermeable membrane 22 such that the osmotic composition 16causes delivery of the drug formulation 14 at a desired rate over apreselected period of time. Preferably, the osmotic composition 16 isformed as one or more osmotic tablets formed of an initially solid ornonflowable composition. However, the osmotic composition 16 included inan osmotic pump 10 according to the present invention is not limited toa tableted and initially solid or nonflowable composition. The osmoticcomposition 16 loaded into a reservoir 12 of an osmotic pump 10according to the present invention may be formed in any suitable shape,texture, density, and consistency. For example, instead of a solid,tableted composition, it is possible that the osmotic composition 16 maybe loaded into the reservoir 12 as a powdered material.

The osmotic composition 16 includes an osmotic agent. The osmotic agentincluded in the osmotic composition is a water-attracting agent thatserves to draw water into the osmotic pump 10 through the semipermeablemembrane 22 and drive the flow of drug formulation 14 out from theosmotic pump 10. The osmotic agent included in the osmotic composition16 may be an osmagent, an osmopolymer, or a mixture of the two. Methodsand formulations for providing osmotic compositions that are suitablefor use in an osmotic pump according to the present invention are wellknown. For example, the patent references that are cited andincorporated by reference herein detail methods and materials suitablefor forming osmotic compositions that may be used in an osmotic pump 10according to the present invention.

Materials that fall within the category of osmagent include materialsthat are nonvolatile, soluble in water, and create an osmotic gradientsuitable for driving the influx of water into the osmotic pump 10.Examples of osmagents that may be useful in the osmotic composition 16of an osmotic pump 10 of the present invention include, but are notlimited to, magnesium sulfate, magnesium chloride, sodium sulfate,lithium sulfate, sodium phosphate, potassium phosphate, d-mannitol,sorbitol, inositol, urea, magnesium succinate, tartaric acid, raffinose,and various monosaccharides, oligosaccharides, and polysaccharides, suchas sucrose, glucose, lactose, fructose, and dextran, as well as mixturesof any of these various species.

Materials that fall within the category of osmopolymer are hydrophilicpolymers that swell upon contact with water. Osmopolymers may be natural(i.e., of plant or animal origin) or synthetic, and examples ofosmopolymers are well known in the art. Particular osmopolymers that maybe used in the osmotic composition 16 of an osmotic pump 10 of thepresent invention include, but are not limited to, poly(hydroxy-alkylmethacrylates) with molecular weights of 30,000 to 5,000,000,poly(vinylpyrrolidone) with molecular weights of 10,000 to 360,000,anionic and cationic hydrogels, polyelectrolyte complexes, poly(vinylalcohol) having low acetate residual, optionally cross linked withglyoxal, formaldehyde or glutaraldehyde and having a degree ofpolymerization of 200 to 30,000, a mixture of methyl cellulose, crosslinked agar and carboxymethylcellulose, a mixture of hydroxypropylmethylcellulose and sodium carboxymethylcellulose, polymers ofN-vinyllactams, polyoxyethylene-polyoxypropylene gels,polyoxybutylene-polyethylene block copolymer gels, carob gum,polyacrylic gels, polyester gels, polyurea gels, polyether gels,polyamide gels, polypeptide gels, polyamino acid gels, polycellulosicgels, Carbopol® acidic carboxy polymers having molecular weights of80,000 to 200,000, Polyox Polyethylene oxide polymers having molecularweights of 10,000 to 5,000,000, starch graft copolymers, and Aqua-Keeps™acrylate polymer polysaccharides.

In addition to an osmotic composition 16, an osmotic pump 10 accordingto the present invention may also include an additive or filler 28distributed around the osmotic composition 16. This filler 28 may be anyflowable composition, such as a liquid or gel composition, which issubstantially incompressible, is suitable for use in the intendedenvironment of operation, is compatible with the other components of theosmotic pump, works to displace air or gas from around the osmoticcomposition 16, and does not cause the osmotic composition 16 to swelland freeze-up, as described in U.S. Pat. No. 6,132,420. Materials andmethods suitable for providing a filler 28 suitable for use in anosmotic pump according to the present invention are also described inU.S. Pat. No. 6,132,420, the contents of which are herein incorporatedin their entirety by reference.

The use of a filler 28 is particularly helpful where the osmoticcomposition 16 is formed as a tableted composition. Machining andtableting tolerances require that there be a gap between the osmoticcomposition 16 and the surrounding reservoir wall 20. Smallirregularities in the shape or contour of the tableted material may alsocreate a gap between the osmotic composition 16 and a piston 18 includedin an osmotic pump 10 according to the invention. Such gaps, which cantypically range from between about 0.001 to 0.1 inches, are filled withair or other gaseous material, and even the smallest of such air gapscan create a start-up delay of several days to weeks. Additionally,air-filled gaps problematically affect the delivery rate of drugformulation when the osmotic pump is subjected to different externalpressures, such as when a patient with an implanted osmotic pump scubadives or travels to higher altitudes. The inclusion of a filler 28serves to reduce or eliminate the extent to which any gaps around theosmotic composition 16 are filled with air or another gaseous materialand, thereby, works to reduce or eliminate the delays and drug deliveryinconsistencies that such gaps can produce.

The movable piston 18 included in an osmotic pump 10 according to thepresent invention is configured to fit within the reservoir 12 in asealed manner that allows the piston 18 to be displaced within thereservoir 12 as water is taken into the osmotic composition 16 and theosmotic composition 16 expands. In a preferred embodiment, the piston 18is formed of a substantially noncompressible material. Moreover, apiston 18 suitable for use in an osmotic pump 10 of the presentinvention is preferably formed of a material that is impermeable to theosmotic composition 16 and the drug formulation 14, and may include oneor more protrusions, which work to form a seal between the piston 18 andthe wall 20 of the reservoir 12. Materials suitable for use in a piston18 included in an osmotic pump 10 of the present invention includemetallic materials, such as metal alloys, elastomeric materials, such asthe nonreactive polymers already mentioned herein, as well as elastomersin general, such as polyurethanes, polyamides, chlorinated rubbers,styrene-butadiene rubbers, and chloroprene rubbers.

As can be seen by reference to FIG. 1, the delivery orifice 24 includedin an osmotic pump 10 of the present invention may simply include anorifice formed through one end of the wall 20 of the reservoir 12. Sucha delivery orifice 24 can be provided using, for example, known moldingmethods or known mechanical or laser drilling methods. If desired, thereservoir 12 of an osmotic pump 10 of the present invention may includemore than one delivery orifice 24. In an alternative embodiment, thedelivery orifice 24 of an osmotic pump 10 of the present invention maybe formed by an outlet plug (not illustrated) that is positioned atleast partially within the reservoir 12. Such an outlet plug may beconfigured, for example, to provide a delivery orifice 24 that optimizesflow of drug formulation 14 or to regulate back diffusion ofenvironmental fluids into the osmotic pump 10. Where the deliveryorifice 24 of the osmotic pump 10 of the present invention is formed byan outlet plug, however, the outlet plug is prepared from asubstantially noncompressible material. Outlet plugs suitable forapplication in an osmotic pump according to the present invention areknown in the art and are described in, for example, U.S. Pat. Nos.5,985,305, 6,217,906, and 5,997,527, the contents of each of which areherein incorporated in their entirety by reference. The dimensions ofthe delivery orifice 24, in terms of both diameter and length, will varydepending on, among other factors, the type of drug delivered, the rateat which the drug formulation 14 is expelled from the osmotic pump 10,and the environment into which it is to be delivered.

Although osmotic pumps according to the present invention are preferablydesigned for and administered to human or animal physiologicalenvironments, osmotic pumps according to the present invention aregenerally applicable for the delivery of beneficial agents to anenvironment of operation and are not limited in utility to physiologicalenvironments. For example, the osmotic pumps according to the presentinvention may be used in intravenous systems (e.g., attached to an IVpump, and IV bag, or an IV bottle) for delivering beneficial agents toanimals or humans, systems for blood oxygenation, kidney dialysis orelectrophoresis, systems for delivering, for instance, nutrients orgrowth regulating compounds to cell cultures, as well as in pools,tanks, reservoirs and the like. Therefore, the osmotic pump 10 of thepresent invention is applicable to the delivery of beneficial agents ingeneral, and the term “drug” as it is used herein refers to anybeneficial agent that may be delivered to an environment of operationand includes, but is not limited to, medicaments, vitamins, nutrients,biocides, sterilization agents, food supplements, sex sterilants,fertility inhibitors, and fertility promoters. Specific drugs that maybe delivered by osmotic pumps of the present invention are detailed, forexample, in U.S. Pat. Nos. 6,132,420, the contents of which areincorporated herein by this reference. Additional examples of drugs thatmay be delivered by an osmotic pump 10 according to the presentinvention can be found in the other patent references that are cited andincorporated by reference herein.

The drug included in the drug formulation 14 contained within an osmoticpump 10 of the present invention can be present in a wide variety ofchemical and physical forms. At the molecular level, the drug may bepresent as an uncharged molecule, molecular complex, or pharmaceuticallyacceptable acid addition or base addition salts, such as hydrochlorides,hydrobromides, sulfate, laurylate, oleate, and salicylate. Salts ofmetals, amines or organic cations may be used for acidic drug compounds.Derivatives of drugs, such as esters, ethers, and amides can also beused. Moreover, the drug formulation 14 included in an osmotic pump 10according to the present invention may include more than one drug,resulting in an osmotic pump 10 capable of delivering multiple drugsduring its functional lifetime.

The drug formulation 14 included in an osmotic pump 10 according to thepresent invention may include any formulation suitable for delivering adrug from an osmotic pump 10 according to the present invention. Thedrug formulation 14 may be formulated as any flowable composition, suchas a slurry, a suspension, or a solution, capable of delivering thedesired drug to a chosen environment of operation. As desired, the drugformulation 14 included in an osmotic pump 10 according to the presentinvention may include one or more of various ingredients that work toallow delivery of the drug to the desired environment of operation. Inparticular, the drug formulation 14 included in an osmotic pumpaccording to the present invention may optionally include preservatives,such as one or more antioxidants or other stabilizing agent, permeationenhancers, or carrier materials that are application appropriate. Forexample, if the osmotic pump is designed for implantation to a human oranimal subject, any carrier, preservative, or permeation enhancer usedwould be a pharmaceutically acceptable material.

As can be seen by reference to FIG. 1, the vent 26 included in anosmotic pump 10 according to the present invention is formed through thewall 20 of the reservoir 12. The vent 26 may be formed by any suitablemethod, such as by mechanical drilling, laser drilling, molding, or anyother known method that may be used to provide a vent 26 of a desiredsize and shape through the material forming the reservoir 12. The vent26 is positioned in the reservoir 12 of an osmotic pump according to thepresent invention such that, during normal operation, it is sealed fromthe osmotic composition 16 under normal operating conditions. However,the vent 26 is also positioned in the reservoir 12 such that, if thepressure within the osmotic pump 10 reaches a magnitude that causesdisplacement of one or more components, the vent 26 is opened orexposed, allowing the internal pressure of the osmotic pump 10 todissipate before one or more components are separated from the osmoticpump 10.

An osmotic pump 10 according to the present invention preferablyincludes a vent 26 that is initially sealed by the semipermeablemembrane 22. In such an embodiment, the semipermeable membrane 22 isfriction fit within the reservoir 12 and both the reservoir 12 and thesemipermeable membrane 22 are configured such that, as a thresholdpressure is reached within the osmotic pump 10, the semipermeablemembrane 22 is progressively displaced from within the reservoir 12. Asit is used herein, the term “threshold pressure” indicates an internalpressure or range of pressures that will cause the semipermeablemembrane 22 included in the osmotic pump 10 to begin to be displacedwithin the reservoir 12, but will not result in immediate separation ofthe semipermeable membrane 22 from the osmotic pump 10. The materialsand configuration of both the semipermeable membrane 22 and thereservoir 12 may be altered, as desired, to achieve a semipermeablemembrane that is progressively displaced at different thresholdpressures. For instance, the semipermeable membrane 22 may be configuredas a plug with multiple retaining rings (not shown) that function toincrease the threshold pressure of the semipermeable membrane and workto facilitate progressive expulsion once the threshold pressure isreached.

The position of the vent 26 in the reservoir 12 is chosen to provide avent 26 that is effectively sealed by the semipermeable membrane 22during normal operation of the osmotic pump 10. However, the vent 26 isalso positioned to ensure the vent 26 is opened if the internal pressureof the osmotic pump 10 reaches or exceeds the threshold pressure for thesemipermeable membrane 22. As the vent is opened, the osmotic materialincluded in the osmotic composition 16 is released into the environmentof operation, resulting in the dissipation of the internal pressurebelow the threshold pressure required to displace the semipermeablemembrane 22. The positioning of the vent 26 is chosen to ensure ventingof the osmotic composition 16 and dissipation of the internal pressurebefore the semipermeable membrane 22 is displaced to such a degree thatthe semipermeable membrane 22 could separate from the osmotic pump whensubjected to mechanical, chemical, or thermal stresses that are typicalof the chosen environment of operation.

Because the rate at which water is imbibed into an osmotic pump 10according to the present invention depends, at least in part, on thesurface area of the semipermeable membrane 22 that is exposed to theenvironment of operation, the vent 26 included in an osmotic pump 10 ofthe present invention has the potential to affect release rateperformance. Where the osmotic pump 10 according to the presentinvention is configured such that the vent 26 allows aqueous liquid fromthe environment of operation to contact the semipermeable membrane 22during normal operation, the increase in exposed surface area providedby the vent 26 will result in an increase in the rate at which waterpermeates and flows through the semipermeable membrane 22. As a result,an osmotic pump 10 according to the present invention may exhibitrelatively shorter start-up times and relatively faster release rateswhen compared to an osmotic pump that does not include a vent 26 or anosmotic pump that includes a vent that is protected from the environmentof operation. Nevertheless, the liquid permeation rate and release rateperformance of an osmotic pump 10 according to the present invention canbe preselected and controlled through, for example, selection oralteration of the materials used to form the semipermeable membrane, thegeometry of the semipermeable membrane, and the surface area andlocation of the exposed portions of the semipermeable membrane.

In addition, the potential impact that a vent 26 may have on thepermeation or release rate provided by the semipermeable membrane 22 ofthe osmotic pump 10 of the present invention can be mitigated or avoidedaltogether. For example, as the size of the vent 26 included in anosmotic pump 10 according to the present invention decreases, any affectthat the vent 26 has on the permeation rate of the semipermeablemembrane 22 or the release rate of the osmotic pump 10 also decreases.Therefore, in a preferred embodiment, the vent 26 included in an osmoticpump 10 according to the present invention is sized such that the vent26 increases the exposed surface area of the semipermeable membrane 22by less than 1% relative to an identical device that does not includethe vent 26. In an alternative embodiment, the vent 26 included in theosmotic pump 10 of the present invention is formed as a generallyannular orifice that has a diameter of less than 0.01 inches. To avoidaltogether any changes in permeation or release rates that may be causedby the vent 26 included in an osmotic pump 10 of the present invention,the vent 26 may be sealed from the environment of operation by a waterimpermeable material, such as a wax or an oil, that is readily expelledas the vent 26 is opened and osmotic material is released.

FIG. 2 through FIG. 4 illustrate the general function of an osmotic pump10 according to the present invention. Once an osmotic pump 10 of thepresent invention is placed in an environment of operation, aqueousfluid is imbibed through the semipermeable membrane 22 at apredetermined rate into the osmotic composition 16. As can be seen inFIG. 2, as osmotic composition 16 takes up water, the osmoticcomposition 16 expands and acts against the piston 18, driving thepiston 18 through its stroke within the reservoir 12. As the piston 18is driven through its stroke, the drug formulation 14 is expelled fromthe osmotic pump 10 at a controlled rate through the delivery orifice24. Typically, the drug formulation 14 is released from the osmotic pump10 at a rate equal to the rate at which water is imbibed into thesystem, and, as a result, the pressure within the osmotic pump 10remains relatively low as the osmotic pump 10 operates to deliver drugformulation 14 at a controlled rate over time.

After the piston 18 reaches the end of its stroke within the reservoir12 and the drug formulation has been delivered from the osmotic pump 10(shown in FIG. 3), water will continue to be taken up through thesemipermeable membrane 22. As water continues to be taken into theosmotic composition 16, the internal pressure of the osmotic pump 10will continue to build, until the threshold pressure for thesemipermeable membrane 22 is reached. As is shown in FIG. 4, once thethreshold pressure is reached, the semipermeable membrane 22 isdisplaced and the vent 26 is opened or exposed such that the osmoticmaterial included in the osmotic composition 16 is released through thevent 26 and into the environment of operation. As osmotic materials arereleased through the vent 26, the internal pressure of the osmotic pump10 decreases below the threshold pressure, and the displacement of thesemipermeable membrane ceases.

The design of the osmotic pump 10 of the present invention not onlyworks to allow venting of the osmotic composition and dissipation ofinternal pressure, but the design of osmotic pump 10 of the presentinvention allows such performance to be achieved without causing arelease of osmotic material that would result in discomfort orirritation to the subject. In particular, the components of the osmoticpump 10 are designed to be substantially incompressible. As a result,when the pressure within the osmotic pump 10 builds to the extent thatthe vent 26 is opened, there is no decompression that may otherwiseresult in the immediate release of an amount of osmotic material thatcould result in localized irritation or discomfort. Instead, where thevent 26 included in the osmotic pump 10 is opened, the osmoticcomposition 14 will typically be delivered from the osmotic pump 10 at amaximum rate that is equal to the maximum release rate provided by theosmotic pump 10. Moreover, as the osmotic composition 14 is releasedthrough the vent 26, the osmotic composition 14 becomes more dilute anda smaller osmotic gradient is produced across the semipermeable membrane22, resulting in an exponential decrease in the mass of osmotic materialreleased over time. Therefore, in each of its embodiments, the osmoticpump 10 of the present invention not only works to dissipate internalpressure before it becomes undesirably high, but the design of theosmotic pump 10 allows such dissipation to occur in a way that reducesthe risk of discomfort to the subject.

1. An osmotic pump for providing sustained delivery of a beneficialagent, comprising: a reservoir for holding the beneficial agent and anosmotic agent; at least one wall defining a boundary of the reservoir;at least one vent formed through the at least one wall; and animpermeable material positioned to seal the at least one vent, whereinthe at least one vent is sealed from an environment of operation by awater impermeable material that is readily expelled as the at least onevent is exposed to the osmotic agent.
 2. The osmotic pump of claim 1,wherein the at least one vent is sized to increase an exposed surfacearea of the semipermeable membrane by less than 1%.
 3. The osmotic pumpof claim 1, wherein the at least one vent comprises an annular orificehaving a diameter of less than 0.01 inches.
 4. The osmotic pump of claim1, wherein the water impermeable material comprises a wax or an oil. 5.The osmotic pump of claim 1, wherein the water impermeable material isconfigured for progressive expulsion when a threshold pressure in theosmotic pump is reached.
 6. The osmotic pump of claim 1, wherein thereservoir is made of a non-bioerodible material.
 7. The osmotic pump ofclaim 1, wherein the osmotic agent comprises an osmotic tablet.
 8. Theosmotic pump of claim 1, wherein the osmotic agent comprises anosmagent, an osmopolymer, or mixtures thereof.
 9. The osmotic pump ofclaim 1, further comprising a filler distributed within the reservoirand around the osmotic agent.
 10. The osmotic pump of claim 1, furthercomprising a movable piston located in the reservoir and between thebeneficial agent and the osmotic agent.
 11. The osmotic pump of claim10, wherein the movable piston is formed of a noncompressible material.12. The osmotic pump of claim 1, wherein the beneficial agent isselected from the group consisting of medicaments, vitamins, nutrients,biocides, sterilization agents, food supplements, sex sterilants,fertility inhibitors, fertility promoters, and combinations thereof. 13.The osmotic pump of claim 1, wherein the beneficial agent is formulatedas a slurry, a suspension, or a solution.
 14. An implantable osmoticpump for providing sustained delivery of a beneficial agent, comprising:a reservoir for holding the beneficial agent and an osmotic agent; and ameans for venting the osmotic agent out of the reservoir upondisplacement of a water impermeable material when a threshold pressurein the osmotic pump is reached.
 15. The implantable osmotic pump ofclaim 14, wherein the means for venting the osmotic agent comprises avent formed through a reservoir wall.
 16. The implantable osmotic pumpof claim 14, wherein the means for venting the osmotic agent comprises aplurality of vents formed through one or more walls that defineboundaries of the reservoir.
 17. An osmotic pump for providing sustaineddelivery of a beneficial agent, comprising: a reservoir for holding thebeneficial agent and an osmotic agent; at least one wall defining aboundary of the reservoir; at least one vent formed through the at leastone wall; and a means for removably sealing the at least one vent, thesealing means being capable of expulsion from the at least one vent whena threshold pressure in the osmotic pump is reached and capable ofreleasing at least a portion of the osmotic agent from the reservoir.18. The osmotic pump of claim 20, wherein the sealing means comprises awater impermeable material.